# Development of Catalytic Glycosylations and Biologically Important Glycosaminoglycans

> **NIH NIH R35** · WAYNE STATE UNIVERSITY · 2024 · $524,144

## Abstract

PROJECT SUMMARY
The work in this proposal builds on our expertise in catalytic stereoselective glycosylations to result in
efficient synthetic methodologies for construction of the challenging glycosidic bonds. We recently
discovered that readily available phenanthrolines, rigid and planar organic compound with two pyridine
rings fused to a benzene ring, effectively act as nucleophilic catalysts to promote stereoselective 1,2-
cis glycosylation reactions of alcohol nucleophiles with both pyranosyl and furanosyl bromide donors.
The phenanthroline catalytic system provides efficient access to a myriad of 1,2-cis pyranosides and
furanosides bearing the C2-oxygen, -azido and -fluoro functional groups under mild and operationally
simple conditions. The phenanthroline-catalyzed methodologies represent long standing synthetic
challenges for highly desirable glycosylations to generate biologically important oligosaccharides and
glycopeptides to advance an understanding of their biological functions. In this R35 grant, we continue
uncovering the simplicity and versatility of phenanthroline catalysts to provide a new principle for the
stereoselective construction of the challenging α-2-deoxy glycosides. Precisely tailored phenanthroline
catalysts can activate both the alcohol nucleophile and the glycosyl halide electrophile simultaneously.
We will also investigate the dual activation mechanism of the phenanthroline catalysts to control site-
selective coupling of polyol nucleophiles and chemoselective coupling of the hydroxyl of serine residue
in the presence of the thiol of cysteine-containing peptides. Further, we will apply the phenanthroline
catalyst platform to the synthesis of heparan sulfate-like oligosaccharides as inhibitors of heparanase,
which is a druggable target for anticancer therapy. We will also develop the library of heparan sulfate
mimetics with all of the possible O- and N-sulfation motifs from readily available aminoglycosides to
advance an understanding of the role of sulfated glycosaminoglycans in many biological systems. In
particular, we will investigate these structurally well-defined heparan sulfate mimetics as the potential
binders of clinically important fibroblast growth factors.

## Key facts

- **NIH application ID:** 10911784
- **Project number:** 5R35GM149213-02
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Hien M Nguyen
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $524,144
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911784

## Citation

> US National Institutes of Health, RePORTER application 10911784, Development of Catalytic Glycosylations and Biologically Important Glycosaminoglycans (5R35GM149213-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10911784. Licensed CC0.

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